Action Points

Note that these studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

Analysis of a major HIV prevention trial among women suggests that developing drug resistance while using a vaginal ring that delivers antiretroviral medication is not an issue.

Note that on the other hand, a less clinical factor -- domestic violence -- affects how women use the ring and therefore how well they are protected from HIV.

CHICAGO -- Analysis of a major HIV prevention trial among women suggests that developing drug resistance while using a vaginal ring that delivers antiretroviral medication is not an issue.

On the other hand, a less clinical factor -- domestic violence -- affects how women use the ring and therefore how well they are protected from HIV, researchers told reporters at the HIV Research for Prevention conference here.

The findings come from the randomized, placebo-controlled ASPIRE study, which tested the efficacy of a silicon ring that elutes the investigational non-nucleoside reverse transcriptase inhibitor (NNRTI) dapivirine. It's designed to be used for up to a month and then replaced.

But importantly, there was little difference in the rate of resistance to NNRTIs between the arms and no indication of dapivirine-specific resistance, according to Urvi Parikh, PhD, of the University of Pittsburgh

The investigators collected plasma for genotyping at the same time HIV seroconversion was detected, Parikh said, and the virus was sequenced successfully in 164 of the 168 women who acquired HIV.

Of those, 18 had various NNRTI-resistance mutations, but the frequency did not differ significantly: 11.8% among those who had been in the dapivirine arm and 10.4% among those who had been using a placebo ring.

That suggests the resistance was acquired, rather than driven by the drug, she said.

None of the participants had mutations associated with dapivirine resistance, Parikh said.

Teasing out what underlies the finding is "tricky," commented Susan Buchbinder, MD, of the San Francisco health department.

"We know that efficacy was much higher the higher adherence was," she told MedPage Today. "So the fact that they have resistance could just mean they weren't using the ring but we don't know that yet."

"What we know is that the women weren't getting infected by dapivirine-resistant virus," she said.

That's a "good signal," Buchbinder said. What remains up in the air is whether women who got infected but continued to use the ring would develop dapivirine resistance, she added.

A key factor in efficacy, the investigators have shown, was how often the ring was used. An analysis reported in July at the International AIDS Conference found that the benefit was at least 56% and possibly greater than 75% when the device was used consistently

One of the factors that can lead to low rates of use is intimate partner violence, according to Thesla Palanee-Phillips, MMed Sci, PhD, of the University of Witswatersrand in Johannesburg, South Africa.

Every quarter during the study, she and colleagues asked participants about "social harms" associated with study participation or ring use and also recorded spontaneous reports made between the quarterly visits.

They also used dried blood spots to test for adherence of the ring, with a level of at least 95 picograms of dapivirine per milliliter of plasma regarded as a benchmark of consistent adherence.

Only 85 participants said that they were subject to or feared intimate partner violence, Palanee-Phillips said, but they were 1.5 times less likely to be adherent over all and up to 2.5 times less likely if the events were recent.

As well, she said, women who did not report a social harm, 17% met criteria for low adherence, compared with 33% of those who did report such an event.

An early driver of the push for microbicides was the notion that women would be better protected against HIV if they could control the means of protection but Palanee-Phillips said women do not always conceal the use of the ring from their partners.

"Women actually do want their partners to be involved," she told MedPage Today, but that can lead to conflicts and in some cases violence.

The ASPIRE study had support from the NIH. The authors made no disclosures.

Buchbinder made no disclosures.

Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

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